(c) Universität Regensburg
August 10th, 2pm in H53: An exciting lecture you should definitely not miss! Ivo Telley from the Instituto Gulbenkian de Ciência in Oeiras, Portugal, will talk about the physical principles underlying nuclear division.
In Drosophila embryos, zygotic nuclei initially undergo rapid successive divisions without cytokinesis and, therefore, a vast number of nuclei share the same intracellular space in a syncytium. They need to be evenly distributed throughout a large cytoplasmic volume and brought to the cell cortex to form even-sized cells. The regular arrangement of the nuclei is vital to later embryo development, and defects that perturb this distribution are lethal. How the regular nuclear distribution during early divisions is achieved and maintained is an interesting yet unresolved question.
One of Ivo’s main research tracks is to understand the physical principles underlying the regular arrangement and precise positioning of nuclei, and the mechanism that maintain the regularity of the nuclear distribution during perturbations such as nuclear division. He will present new insight into the mechanics of nuclear distribution and point at microtubule-based molecular interactions that are involved in distance maintenance between nuclei. It is known that the microtubule cytoskeleton plays a key role in nuclear transport, and its dynamics is greatly determined by the microtubule-organizing center, the centrosome. Ivo has evidence from mitotic mutants which suggests that the centrosomes, and not the nuclei, are the spatial organizer in the early embryo.
Finally, he will present efforts in developing an extract approach to study young fertilized eggs and visualize pronuclei and sperm in time-lapse and high-resolution, something which has not been possible before. With this approach, he aims to study how Wolbachia infection in Drosophila affects the last stages of fertilization and, in particular, what causes the first mitotic division to fail.
At the Instituto Gulbenkian de Ciência in Oeiras, Portugal, Ivo is head of a multidisciplinary research team interested in the physical aspects of intracellular organization. As a model system, they study the earliest stage of Drosophila development, from the mature egg to fertilization to pre-blastoderm cleavages. They focus on pronuclear fusion in the fertilized egg and how the syncytial embryo defines the inter-nuclear distance between rapid mitotic divisions. They employ reconstitution approaches in egg explants combined with time-lapse light microscopy and image processing while taking advantage of Drosophila genetics. By applying this assay in a study of host-micro-organism interactions, they have started to investigate how Wolbachia infection in Drosophila affects the last stages of fertilization preceding developmental arrest due to cytoplasmic incompatibility.
Did you ever go to a conference addressing a topic well outside your comfort zone? No? Well, then you are missing out on some great and exciting science!
I was recently invited to the German American Frontiers of Engineering (GAFoE) Symposium in Evendale, Ohio, by the Alexander von Humboldt Foundation. The sessions were planned to cover a great diversity of topics ranging from ‘Gene Editing’ to topics that initially sounded rather mysterious to me, like ‘Advanced Manufacturing’, ‘Industry 4.0 vs. Industrial Internet of Things’, and ‘Streams of Water and Information’. To be honest, I was puzzled about the invitation to participate. I didn’t really feel like somebody who could contribute a lot to this meeting. But then I thought why not try something new? I eventually accepted the invitation and that turned out to be a great decision!
In particular the sessions with the rather mysterious titles were the most exciting and fascinating ones to me! Everything was new and every single talk provided me with novel insights into topics that I had so far not really thought about a lot. Looking beyond one’s own nose can sure be a very stimulating and exciting experience! I feel that during this GAFoE meeting from March 31st to April 2nd, 2017, I learned more than in the previous three meetings combined.
But hearing about novel topics is one thing – it was even more exciting to meet the many other, enthusiastic participants. Most of them felt to be non-experts, too, and they were evenly excited to expand their knowledge into the other disciplines. This created a unique atmosphere and stimulated discussions that continued at the hotel bar into the early morning hours.
So, if you ever get invited to a meeting that addresses a topic that appears quite distant to your own research interests, don’t immediately turn down the invitation – rather think about the great opportunity to learn something new and meet new people.
I would like to thank the Alexander von Humboldt Foundation for the invitation and the travel stipend, the National Academy of Engineering, GE aviation for hosting us, and all the organizers for putting together such a great meeting!
Good news! We are happy to announce that our review on the function of the Drosophila RNA-binding protein Sex-lethal (Sxl) was recently accepted. Sxl is particularly interesting: it is a rather small RNA-binding protein with a simple architecture, nonetheless it engages in the regulation of multiple aspects of gene expression to direct female development. The review is open access and can be downloaded here. Let us know what you think about it!
One equals two!
While this simple statement gets most people shaking their heads in disbelief, we geneticists get all excited. It is about dosage compensation – intricate genetic programs that ensure an equal gene dose from different numbers of chromosomes.
Why is that important? Most higher eukaryotes reproduce sexually, allowing them to combine alleles from two different individuals thus increasing variability in the offspring and resulting in the cleansing of harmful mutations from a population. Sexual reproduction usually requires animals of two different sexes: males and females. Although numerous exceptions exist, the two sexes typically differ in the number of X chromosomes. However, it is critical for survival that the genetic output from different numbers of X chromosomes is matched. This poses a big challenge to gene expression. In nature several different strategies have been invented to achieve a comparable gene dose in the two different sexes by either reducing the genetic output from two X chromosomes or by boosting transcription of the single X chromosome.
Drosophila melanogaster has long served as a genetic model system to study dosage compensation in molecular detail. Female flies carry two X chromosomes (XX) and males one (XY). Dosage compensation is achieved by hypertranscription of the single, male X chromosome, essentially doubling its output. But how is this achieved on a molecular level?
On May 23rd, Peter Becker from the Ludwig-Maximilians-University in Munich will talk about how flies assemble a remarkable regulator to boost transcription of the single male X chromosome. Join us at 5p.m. in H53 for exciting science!
From March 13th-15th, the DFG Forschergruppe FOR2333 met at the EMBL in Heidelberg to discuss the latest scientific results. In parallel several workshops were offered that provided hands-on training on various exciting topics including: an introduction to structural biology (by Dierk Niessing and Fulvia Bono), an introduction to bioinformatics (by Kathi Zarnack and Markus Seiler), image analysis (Imre Gaspar), and preparation of scientific figures (by Helena Jambor).
‘During these two very exciting days I have learned a lot and had a great time being part of this wonderful meeting.’ (Rebecca Moschall)
‘A very well organized and extremely helpful course on RNA-Seq analysis featuring top-notch speakers and experts in the field’
– that is how one of the participants summarized the recent bioinformatics course on ‘Analysis of NextGen RNA-Seq data for expression profiling and protein-binding RNAs’ that took place from October 10th to 14th at the University of Regensburg. The Graduate Research Academy RNA Biology hosted several renowned experts in the field that delivered fascinating, public lectures addressing state-of-the-art methods for gene expression profiling and RNP analysis. Afterwards 18 selected participants had the opportunity for some hands-on training on actual datasets. We are happy that so many interested students from seven different universities joined us. And apparently, according to the feedback we got, for the participants the course really did make a difference:
‘with the combination of excellent speakers and target-oriented hands-on training, this one-week course increased my knowledge on current NGS tools and enabled me to analyze my own datasets’
During five intense days, a broad variety of topics was covered. These ranged from practical considerations for setting up sequencing experiments (Stefan Kirsch, Fraunhofer ITEM), Sequence alignment and quality assessment (Steve Hoffmann, Universität Leipzig and Nicholas Strieder, Universität Regensburg), pecularities of high-throughput data analysis (Rainer Spang, Universitt Regensburg), differential gene expression and alternative transcript level analyses (Simon Anders, FIMM Helsinki, Charlotte Soneson, University of Zurich and Grischa Tödt, EMBL Heidelberg) to probing of RNPs (CLIP, Markus Hafner, NIH Bethesda) and translation (Ribosomal Profiling, Jan Medenbach, Universität Regensburg).
We are extremely grateful to the instructors and tutors and would like to thank all of them for their generous support! Their help, commitment, dedication, and willingness to share knowledge made a real difference and the course a big success!
In December we will have another great talk: Elmar Wahle from the Martin-Luther Universität Halle-Wittenberg will present exciting findings regarding ‘Post-transcriptional regulation of maternal mRNA during early embryonic development: The nanos mRNA of Drosophila‘.
During the early development of animal embryos, the zygotic nucleus is not transcribed. Instead, protein synthesis is driven by maternal mRNAs that were synthesized during oocyte development and stockpiled in an inactive state. Thus, regulation of protein synthesis in early embryos is post-transcriptional. A prominent example is the nanos mRNA of Drosophila, regulation of which is essential for the formation of the anterior-posterior axis of the embryo (see also here). Synthesis of the Nanos protein is driven by small fraction of nanos mRNA that is localized at the posterior pole. The bulk of nanos mRNA is distributed uniformly throughout the embryo and is translationally repressed and decays gradually.
Elmar and his team are investigating the mechanisms controlling translational repression and degradation of the non-localized nanos mRNA. Some of the proteins that they have identified as constituents of the repressor complex are universally involved in translational repression and mRNA degradation, suggesting that their findings may have significance beyond the regulation of maternal mRNAs.
So mark your calendar and join us for exciting science on December 8th at 2p.m. in H53!
On tuesday next week, Jean Yves Roignant from the institute of Molecular Biology (IMB) in Mainz will present intriguing findings that highlight the importance of m6A RNA modification in flies.
N6-methyladenosine RNA (m6A) is a prevalent mRNA modification in vertebrates. While its functions in the regulation of posttranscriptional gene expression are beginning to be unveiled, the precise roles of m6A during development of complex organisms remain unclear. Jean-Yves and his team have carried out a comprehensive molecular and physiological characterization of the individual components of the methyltransferase complex as well as of the YTH nuclear reader protein in Drosophila melanogaster. They identified the member of the split ends protein family, Spenito, as a novel bona fide subunit of the methyltransferase complex. Furthermore, they demonstrated important roles of this complex in neuronal function and sex determination, and implicate the nuclear YT521-B as a main m6A effector in these processes. Altogether, this work substantially extends our knowledge on m6A biology, demonstrating the crucial functions of this modification in fundamental processes within the context of the whole animal.
Mark your calendar – there will be an exciting talk on October 20th! Dierk Niessing (affiliated with both the Biomedical Center of the Ludwig-Maximilians-University Munich and the Institute of Structural Biology of the Helmholtz Zentrum Munich) will present fascinating data on how RNPs assemble and how mRNA localization is achieved.
In eukaryotes asymmetric localization of mRNAs and their local translation is a universal mechanism to generate cellular asymmetry. It is required for diverse processes such as embryogenesis, stem cell division and differentiation of somatic cells. For localization the transcripts are selectively recognized by motor-protein containing particles and actively transported along the cytoskeleton. Despite its importance, the molecular basis of this spatial and temporal control of gene expression is not well understood. The Niessing lab took advantage of the fact that mRNA localization in budding yeast involves considerably fewer core factors than in higher eukaryotes. In S.cerevisiae the ASH1 mRNA and about 30 other transcripts are actively transported from the mother to the daughter cell by a myosin-containing complex. At the tip of the daughter cell ASH1 mRNA then becomes locally translated.
Employing biochemical, biophysical and structural approaches, Dierk’s lab has studied in molecular detail the assembly of all core components of the ASH1 mRNA-transport complex. Moreover, they have succeeded to in vitro reconstitute transport complexes, motile particles with the size of about 1mDa, and characterized key features of their biogenesis and activation. Together these insights serve as one of the best-understood examples of how cells generate cellular asymmetry on the molecular level.
Dierk is a full professor at the Biomedical Center of the Deptartment of Cell Biology at the Ludwig-Maximilians-University Munich and deputy director of the Institute of Structural Biology of the Helmholtz Zentrum München. He is also the speaker of the recently funded DFG Research Unit FOR2333 ‘Macromolecular Complexes in mRNA Localization’, a multidisciplinary research consortium that addresses principles of gene regulation by directional RNA transport and local translation.
The second meeting of the DFG funded Research Unit FOR2333 ‘Macromolecular Complexes in mRNA Localization’, took place from September 2nd to 5th in the wonderful city of Duesseldorf in North Rhine-Westphalia. Exciting research was presented from all participating labs (Bethune, Bono, Ephrussi, Feldbrügge, Jansen, Kiebler, Niessing, and Zarnack – in alphabetical order) and the associated mentee Inga Lödige. I am very happy for the invitation to participate in this wonderful meeting and for being given the opportunity to present some of our recent progress in the nanos project. Michael Feldbrügge and his team were wonderful hosts, organizing additional social activities that stimulated scientific discussions – of course while enjoying the famous local ‘Alt’-beer.
(picture courtsey of Dierk Niessing)
Are circular RNAs (circRNAs) translated? It is very intriguing to speculate that (at least some) circRNAs might encode functional peptides. So far however, evidence in support of this theory is weak. One might hypothesize that by non-canonical initiation once in a while a ribosome might indeed translate an open reading frame encoded by circular RNA, whether this yields significant amounts of a functional protein still remains to be demonstrated.
In a collaborative effort with the Bindereif lab at the Justus-Liebig-University of Giessen, we have analyzed the sedimentation of circRNAs in sucrose gradients. If circRNAs are indeed translated this could be revealed by a change of sedimentation behavior after treatment with a drug that releases elongating ribosomes from RNAs (Puromycin). In our experiments however, no significant change in sedimentation behavior of selected abundant circRNPs from HeLa cells could be observed, suggesting that these circRNAs are not (or at best only weakly) translated.
CircRNAs do however associate with proteins to form ribonucleoproteins (RNPs). In our recent publication ‘CircRNA-protein complexes: IMP3 protein component defines subfamily of circRNPs’ (published in Scientific Reports) we demonstrate that in HeLa cells, circRNAs form distinct, large RNPs. Moreover, we identify the RNA-binding protein and tumor marker IMP3 (IGF2BP3) as a protein component of numerous circRNPs.
(Picture taken from Schneider et al., 2016, Scientific Reports 6, 31313, doi:10.1038/srep31313, CC 4.0)
The ‘Sino-German Symposium on RNA Biology and human disease: from Molecular Mechanisms to Global Networks‘ took place from July 25-27 at the beautiful castle ‘Schloss Rauischholzhausen’ in the middle of Hessia. Albrecht Bindereif (Justus-Liebig-University of Giessen, Germany) and Zefeng Wang (CAS-MPG Partner Institute for Computational Biology, Shanghai, P.R. China) invited more than 30 participants from China and Germany to discuss the latest findings in RNA biology and to forge scientific sino-german collaborations. A great symposium and a great experience, meeting old and new colleagues from China and making new friends.
Many thanks to Jingyi Hui (IBCB Shanghai) for the translation into chinese! Picture courtsey of Silke Schreiner, University of Giessen
RNA 2016 – The 21st annual meeting of the RNA Society and the 18th annual meeting of the RNA Society of Japan took place in the lovely city of Kyoto from June 28th to July 2nd. It was a very exciting meeting in the former imperial capital of Japan. Brilliant keynote lectures and more than 20 sessions packed with exciting talks covered the entire field of RNA biology, providing the participants with a broad overview as well as exciting novel developments in RNA-based research. All this was complemented with tours to the cultural highlights of the surrounding city. A brilliant experience!
After this wonderful conference it is clear that I have to attend the next meeting of the RNA Society, too, which will take place in Prague from May 30th to June 3rd 2017. Looking forward to seeing you there!
A special issue from Pflügers Archiv – European Journal of Physiology focusing on the role of RNA in physiology and disease has just been published. It features review articles – many of which are open access – that address diffenrent aspects of and the latest findings in RNA biology. So take some time and indulge yourself with some exciting reading!